1. Field of the Invention
The field of the invention is transcription factors, particularly zinc finger transcription factors, and more particularly transcription factors involved in the expression of RANTES.
2. Background of the Invention
Transcription factors are proteins that play a critical role in the regulation of eukaryotic gene expression. Transcription factors regulate expression of a gene by binding to sequence motifs positioned at various locations relative to the gene, where the resultant binding event modulates expression of the gene. Because of their role in the regulation of gene expression, the identification of transcription factors is of great interest in both research and industry as such factors are potential targets for therapeutic agents.
RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted) is a member of the large and growing family of immunoregulatory cytokines called chemokines. The functions of chemokines include attracting blood leukocytes to sites of inflammation, regulating leukocyte maturation, trafficking and homing, and the development of lymphoid tissues. RANTES belongs to the Cxe2x80x94C chemokine subfamily. It is a potent chemotactic agent for monocytes, T lymphocytes, basophils, and natural killer cells. It also causes degranulation of basophils, respiratory burst in eosinophils, and activation of T cells. Thus, RANTES appears to play an important role in both acute and chronic phases of inflammation.
RANTES and the closely related chemokines, macrophage inflammatory protein 1xcex1 (MIP-1xcex1) and MIP-1xcex2, may also play a role in resistance to human immunodeficiency virus (HIV) infection. It has been shown that RANTES, MIP-1xcex1, and MIP-xcex2 inhibit infection of HIV in CD8+ T cells in vitro, and that these chemokines are highly expressed in some patients who are HIV+ but do not progress to AIDS. It has also been shown that the Cxe2x80x94C chemokine receptor CCxe2x80x94CKR5, which selectively binds to these chemokines, is a co-receptor for HIV entry into target cells.
In normal T cells, expression of the RANTES gene is xe2x80x9clate,xe2x80x9d occurring three to five days after activation. In the context of an immune response, late RANTES expression may be important in amplification and propagation of an inflammatory state. However, little is known about the molecular mechanisms underlying the induction of genes at this late stage of T cell activation.
Because RANTES plays a pivotal role in both acute and chronic inflammation and can block HIV infection in vitro, understanding the molecular basis for control of RANTES gene expression, especially in T cells, is of great interest.
Relevant Literature
Patent documents of interest include: WO 97/00266; 5,840,544 and 5,652,133.
Also of interest are: Nelson and Krensky, Current Opinion in Immunology (1998) 10: 265-270 and Baggiolini, Nature (1998) 392: 565-568.
A novel zinc finger transcription factore (RFLAT-1) and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including diagnostic and therapeutic agent screening applications, as well as in treatment therapies. Also provided are methods of treating disease conditions associated with RANTES function, e.g. inflammation, and the like.